Beecham Group Plc

Smithkline Beecham Corporation

Lee James Beeley

Peter M Newsome

John M Berge

Stephen F Moss

David Kenneth Dean

John Michael Berge

Mervyn Thompson

Robert William Ward

Richard Lewis Jarvest

Geoffrey H Baker

Nikesh R Kotecha

Robert James Godden

Kelly Paine

Richard Anthony Godwin Smith

Malcolm N Burgess

The present invention provides a protein fragment of the ob protein, being an active site of the protein. The active site is suitably provided by the ob protein when it is in the form of a four helix bundle structure, particularly that having an up-up down-down topology. In particular, the active site is formed from one or more amino acids selected from one or more of the four helices forming the secondary stucture of the ob protein, especially a protein fragment consisting of amino acid residues 26 to 39, 74 to 88, 93 to 113 or 142 to 161. The compounds of the invention arc considered to be capable of regulating the physiological activity of the ob protein and are therefor of potential use in the treatment of nutritional and metabollic disorders, particularly obesity and diabetes in the case of agonists and anorexia and cachexia in the case of antagonists.

Biologically active peptide of ob protein

HNFCW60 polypeptides and polynucleotides and methods for producing such polypeptides by recombinant techniques are disclosed. Also disclosed are methods for utilizing HNFCW60 polypeptides and polynucleotides in the design of protocols for the treatment of obesity, diabetes, hyperlipademia and body weight disorder, among others, and diagnostic assays for such conditions.

Polynucleotides and polypeptides belonging to the uncoupling proteins family

Heterocyclic ethanolamine derivatives with .beta.-adrenoreceptor

A compound of formula (I): ##STR1## or a pharmaceutically acceptable salt, or solvate thereof, wherein,

Derivatives of 4-(2-aminoethyl)phenoxymethyl-phosphonic and -phosphinic

##STR1## A compound of formula (I) or a pharmaceutically acceptable salt, ester or amide thereof, or a pharmaceutically acceptable solvate thereof, wherein R.sup.0 represents a substituted or unsubstituted aryl group; R.sup.1 represents hydrogen or an alkyl group; R.sup.2 represents a moiety of formula (a) wherein R.sup.4 and R.sup.5 each independently represent hydrogen, alkyl, hydroxyalkyl, cycloalkyl or R.sup.4 together with R.sup.5 represents (CH.sub.2).sub.n wherein n is 2, 3 or 4; T represents hydrogen, nitrile or a group --CO.R.sup.s wherein R.sup.s represents hydroxy, alkoxy or a group --NR.sup.t R.sup.u wherein R.sup.t and R.sup.u independently represent hydrogen, alkyl or R.sup.t and R.sup.u together with the nitrogen to which they are attached represent a saturated heterocyclic group; and R.sup.3 represents hydrogen, halogen, alkyl or alkoxy; a process for the preparation of such a compound, a pharmaceutical composition comprising such a compound and the use of such a compound in medicine.

Phosphonated arylethanolamine compounds with anti-hyperglycemic and/or

A compound of formula (I): ##STR1## or a pharmaceutically acceptable salt, ester or amide thereof, or a pharmaceutically acceptable solvate thereof, wherein:

Heterocyclic compounds which have useful pharmaceutical utility

Imidazole substituted compounds which have useful pharmaceutical utility

A compound of formula (I): ##STR1## or a pharmaceutically acceptable salt, ester or amide thereof, or a pharmaceutically acceptable solvate thereof, wherein: Z represents a residue of a substituted or unsubstituted aryl group, A.sup.1 represents a substituted or unsubstituted methylene group or a substituted or unsubstituted ethylene group; A.sup.2 represents a substituted or unsubstituted methylene group or a substituted or unsubstituted ethylene group; providing that at least one of A.sup.1 or A.sup.2 represents a substituted methylene group or a substituted ethylene group, X represents O or NR.sup.o wherein R.sup.o represents a hydrogen atom, a substituted or unsubstituted alkyl group, a substituted or unsubstituted aryl group, an alkanoyl group substituted or unsubstituted in the alkyl moiety, or an arylalkyl moiety substituted or unsubstituted in the aryl moiety, p represents an integer 2 or 3, and q represents an integer in the range of from 1 to 12; a process for preparing such a compound, a composition comprising such a compound and the use of such a compound in medicine.

4,5 Dihydroimidazole compounds which have useful pharmaceutical utility

A compound of formula (I): ##STR1## or a pharmaceutically acceptable acid addition salt and/or a pharmaceutically acceptable solvate thereof, wherein A represents a residue of a benzene ring optionally having up to four substituents selected from the group consisting of halogen, C.sub.1-6 alkyl aNd C.sub.1-6 alkoxy; R.sup.1 and R.sup.2 each independently represent a hydrogen atom or a C.sub.1-6 alkyl group; X represents a bond or a moiety CHR.sup.1 wherein R.sup.1 is as defined above; and Z represents O, NH or S.

Dihydro-indene-amine-dihydrooxazoles

Compounds of formula (I): ##STR1## or a salt or acyl derivative thereof; wherein

Benzylideneamino- and phenylacetylguanidines and their pharmaceutical

A compound of formula (I): ##STR1## or a salt thereof wherein R.sup.1 is halogen, C.sub.1-4 alkyl or C.sub.1-4 alkoxy

Amidines

Compounds A--B--C wherein A is 2 imidazolinyl or N-alkyl derivative thereof, B is oxygen, sulphur, CR.sup.1 R.sup.2 wherein R.sup.1 and R.sup.2 are hydrogen or alkyl, or NR.sup.3 wherein R.sup.3 is hydrogen or alkyl, and C is a 5- or 6- membered carbo- or heterocyclic group having a nitrogen containing substituent and up to two other substituents, are useful in treatment of diarrhoea or scours. Certain compounds A--B--C are novel.

Treatment of diarrhoea with 2-aminoimidazoline derivatives

Compounds of formula (I): ##STR1## wherein R.sup.1 and R.sup.2 are the same or different and each is selected from halogen, alkyl, haloalkyl, alkoxy and alkoxyalkyl,

Quaternary amino imidazolidines, compositions and use

Compounds A - B - C wherein A is 2 imidazolinyl or N-alkyl derivative thereof, B is oxygen, sulphur, CR.sup.1 R.sup.2 wherein R.sup.1 and R.sup.2 are hydrogen or alkyl, or NR.sup.3 wherein R.sup.3 is hydrogen or alkyl, and C is a 5 - or 6 - membered carbo- or heterocyclic group having a nitrogen containing substituent and up to two other substituents, are useful in treatment of diarrhoea or scours. Certain compounds A - B - C are novel.

Growing community of inventors

Dorking, United Kingdom

Lee James Beeley